Cau, Stefany B. A.

Tostes, Rita C.

English

PubMed

Stefany B. A. Cau

Rita C. Tostes

Frontiers - Publisher Connector

General Commentary
published: 22 February 2012
doi: 10.3389/fphys.2012.00031
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Ming, X.-F., Montani, J.-P., and Yang, Z. (2012). 
Perspectives of targeting mTORC1-S6K1 in car-
diovascular aging. Front. Physiol. 3:5. doi: 10.3389/
fphys.2012.00005
Vezina, C., Kudelski, A., and Sehgal, S. N. (1975). 
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Received: 11 January 2012; accepted: 06 February 2012; 
published online: 22 February 2012.
Citation: Cau SBA and Tostes RC (2012) mTOR inhibi-
tion: a promise for a young heart. Front. Physio. 3:31. doi: 
10.3389/fphys.2012.00031
This article was submitted to Frontiers in Vascular 
Physiology, a specialty of Frontiers in Physiology.
Copyright © 2012 Cau and Tostes. This is an open-access 
article distributed under the terms of the Creative Commons 
Attribution Non Commercial License, which permits non-
commercial use, distribution, and reproduction in other 
forums, provided the original authors and source are 
credited.
It has been hypothesized that some 
dietary regimes, like caloric restriction and 
methionine restriction, extends lifespan by 
decreasing mTOR activity (Kaeberlein et al., 
2005). Accordingly, a comparison between 
the beneficial effects of pharmacological 
intervention with rapamycin and life style 
modification (caloric restriction) is also 
provided by the authors. One should keep 
in mind that the effects produced by caloric 
restriction and inhibition mTOR signaling 
are not straightforward correlated. Unlike 
caloric restriction, rapamycin treatment does 
not reduce animal size (Harrison et al., 2009) 
and caloric restriction fails to extend life span 
when initiated late in life (Masoro, 2005).
Mammalian target of rapamycin–S6K1 
signaling and its specific inhibition emerge 
as a promising “treatment for aging,” mainly 
through the prevention or reversion of car-
diovascular aging. However, only intense 
research will clarify whether potential 
adverse side effects of mTOR inhibitors, such 
as suppression of the immune system (Weir 
et al., 2010), impairment of glucose toler-
ance (Houde et al., 2010), can be overcome 
by the beneficial effects in the treatment of 
age-related diseases (especially if they are to 
be used as a prophylactic treatment). Future 
research targeting mTOR downstream pro-
teins, which would exhibit more specific 
actions, will also clarify the relevance of 
mTOR inhibition for the prophylactic treat-
ment of aging or age-related diseases.
RefeRences
Brown, E. J., Albers, M. W., Shin, T. B., Ichikawa, K., Keith, 
C. T., Lane, W. S., and Schreiber, S. L. (1994). A mam-
malian protein targeted by G1-arresting rapamycin-
receptor complex. Nature 369, 756–758.
A Commentary on
Perspectives of targeting mTORC1–S6K1 in 
cardiovascular aging
by Ming, X.-F., Montani, J.-P., and Yang, 
Z. (2012). Front. Physiol. 3:5. doi: 10.3389/
fphys.2012.00005
The mammalian target of rapamycin 
(mTOR) is a serine/threonine kinase 
that senses nutritional and cellular 
energy status and regulates cell growth, 
proliferation, and survival. Rapamycin 
(sirolimus), a naturally occurring anti-
fungal macrolide isolated from the bac-
terium Streptomyces hygroscopicus in a soil 
sample from Easter Island of the Pacific 
Ocean (or Rapa Nui in the native lan-
guage; Vezina et al., 1975), inhibits mTOR 
interaction with other molecular compo-
nents (Brown et al., 1994). Rapamycin was 
shown to extend life span in mice, even 
when administered late in life (Harrison 
et al., 2009), suggesting that inhibition of 
the mTOR pathway may prolong human 
life span.
In this review, Ming et al. (2012) 
address the role of mTOR complex 1 and 
its downstream effector S6K1 (mTORC1–
S6K1) signaling pathway in aging and age- 
associated diseases. The authors discuss the 
important new concept that augmented 
mTORC1–S6K1 signaling is not only 
critical in aging-related processes, but also 
provides a link between aging and cardio-
vascular disturbances, such as vascular and 
cardiac remodeling seen, e.g., in diabetes, 
arterial hypertension, atherosclerosis, and 
heart failure.
mTOR inhibition: a promise for a young heart
Stefany B. A. Cau and Rita C. Tostes*
Department of Pharmacology, Medical School of Ribeirao Preto, Ribeirao Preto, São Paulo, Brazil
*Correspondence: rtostes@usp.br
www.frontiersin.org February 2012 | Volume 3 | Article 31 | 1


mTOR Inhibition: A Promise for a Young Heart

Stêfany Bruno De Assis Cau

Rita C Tostes

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mTOR inhibition: a promise for a young heart.

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mTOR Inhibition: A Promise for a Young Heart

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